Increased Breast Cancer Mortality Research Articles

Abstract PO3-16-07: Strategies to Enact for Equitable and Unbiased Care of Black, Triple Negative Breast Cancer Patients

Abstract Background: Black women are at higher risk for early onset and increased breast cancer mortality, especially from the sub-type Triple-Negative Breast Cancer (TNBC), than their white peers. A patient experience survey has not been implemented or published for Black women diagnosed with TNBC. Tigerlily Foundation (TLF) conducted a TNBC survey of BIack women to understand the patient experience throughout the cancer continuum of care. Methods: The survey instrument received an IRB exception and included 40 questions organized by the following themes: Demographics, Self-Detection/Early Assessment, Screening to Diagnosis, Diagnosis to Treatment, Post Treatment and Palliative Care/Survivorship, Emotional Trauma and Mental Health, and Trust/Bias. Data collection occurred between December 2022 and January 2023. Two methodological approaches influenced this innovative study design: 1) a Health Literate and Culturally Sensitive approach and 2) a Trusted Outreach approach. The survey was sent to leaders of patient-based organizations who shared the TLF survey with their constituents. Results: All participants (N = 106) racially identified as Black women diagnosed with TNBC. The age of participants ranged from 25 – 71. Participants were not always given information to manage their expectations before or after the screening process, as 38% reported they did not receive such information, while 45% reported they did. The number of times participants required diagnostic imaging ranged from only once (24%), two-three times (41%), four-five times (17%), or greater than six times (11%). Biopsies also varied among participants from one (25%), two-three times (40%), four-five times (15%), or greater than six times (8%). Biomarker testing was not equitably offered to all participants, as 30% reported they were not given the opportunity, while 48% were given the choice. While most participants reported a good understanding of their prognosis and treatment options (59%), other participants shared that the information they received could have been better (26%). Others stated they were given zero information to work with (15%). Many participants experienced a diagnosis change, and 57% were initially diagnosed with a different breast cancer subtype, while 24% were initially diagnosed with TNBC. Conclusions: Prospective implementation science is needed to ensure equitable care standards are sustainably provided to Black women. It is imperative to understand the cancer care continuum from the perspective of the patients, what they think of the care received. Equally important, it is necessary to know what education, resources and care the patients would have liked to receive before or upon diagnosis. Health equity is not achieved based on EHR, county-level beneficiary data, or SEER data alone. Gathering information regarding the patients' experience is a factor in achieving health equity. TLF successfully reached Black TNBC patients to share their authentic experiences and provided a framework for other research institutions and patient advocacy groups to do the same. Citation Format: Virginia Leach, Jeanne Regnante, Maimah Karmo, Shanda Cooper, Krista Peoples, Lizzie Wittig. Strategies to Enact for Equitable and Unbiased Care of Black, Triple Negative Breast Cancer Patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-16-07.

“How can a woman live without having a breast?”: challenges related to mastectomy in Ethiopia

BackgroundAlthough mastectomy is the standard treatment modality for breast cancer patients in Ethiopia, our previous study revealed that one in five patients do not receive the recommended procedure, half due to patient refusal or lack of returning to the hospital. Therefore, this study aimed to explore reasons for refusing mastectomy and identify challenges among breast cancer patients in Ethiopia.MethodsAn explorative qualitative study was conducted in four hospitals located in the towns of Woliso, Butajira, Hossana, and Assela. A total of 14 in-depth interviews (IDIs) and eight focus group discussions (FGDs) were held with breast cancer patients, patient relatives, and health professionals. Four semi-structured interview guides were used to facilitate the IDIs and FDGs. All recorded IDIs and FGDs were transcribed and translated verbatim and entered in NVivo 12 software. Emerging ideas were categorised and explained using an inductive content analysis approach.ResultsOur participants reported that particularly elderly and very young women refuse to have mastectomy. The main reasons identified in this study were summarised into six themes: (i) fear of the surgical procedure, (ii) religious beliefs and practice, (iii) utilisation of traditional treatments, (iv) in relation to having a baby and breastfeeding their children (young patients often request to remove only the lump, leaving their breast tissue intact), (v) lack of awareness about the disease, and (vi) sociocultural factors and advice from the community that influence women, since breasts are considered an attribute of femininity, beauty, and motherhood. In addition, knowing someone who died after mastectomy emerged as a main reason for not having breast cancer surgery.ConclusionsHigh refusal rate for mastectomy has direct implication on increased breast cancer mortality. Hence, expansion of radiotherapy service is instrumental to initiate breast-conserving surgery as an alternative surgical procedure, especially for young women with early-stage breast cancer. Involving religious leaders, traditional healers, and breast cancer survivors could be an effective strategy to persuade newly diagnosed breast cancer patients. Addressing individual patient psychosocial needs and preferences may substantially improve retention of breast cancer patients in the health system.

A Comparison of Three Area-Level Indices of Neighborhood Deprivation and Socioeconomic Status and their Applicability to Breast Cancer Mortality.

Neighborhood deprivation indices are widely used in research, but the performance of these indices has rarely been directly compared in the same analysis. We examined the Area Deprivation Index, Neighborhood Deprivation Index, and Yost index, and compared their associations with breast cancer mortality. Indices were constructed for Georgia census block groups using 2011-2015 American Community Survey data. Pearson correlation coefficients and percent agreement were calculated. Associations between each index and breast cancer mortality were estimated among 36,795 women diagnosed with breast cancer using Cox proportional hazards regression. The indices were strongly correlated (absolute value of correlation coefficients > 0.77), exhibited moderate (41.4%) agreement, and were similarly associated with a 36% increase in breast cancer mortality. The similar associations with breast cancer mortality suggest the indices measure the same underlying construct, despite only moderate agreement. By understanding their correlations, agreement, and associations with health outcomes, researchers can choose the most appropriate index for analysis.

Abstract B077: Understanding the relationship between neighborhood deprivation and breast cancer mortality among Black and White women

Abstract Background: Neighborhood deprivation has been associated with increased breast cancer mortality among White women, but findings are inconsistent among Black women, who are more likely to die from the disease. To improve our understanding of the relation, we investigated the joint effects of race and neighborhood racial composition, residential mobility, and rurality on the neighborhood deprivation-breast cancer mortality association among White and Black women. Methods: In 2010-2017, 31,358 non-Hispanic White and Black women diagnosed with invasive stage I-IIIA breast cancer were identified by the Georgia Cancer Registry and were followed through 2019 for breast cancer mortality. The neighborhood deprivation index (NDI) was derived through principal component analysis of 2011-2015 block group-level American Community Survey (ACS) data on poverty, income, housing, unemployment, occupation, and education. Neighborhood racial composition and residential mobility were measured using 2011-2015 ACS data. Rurality was measured using Georgia Department of Public Health data. We used Cox proportional hazards regression to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for the association between NDI, in quintiles, and breast cancer mortality, overall and according to joint effects of race and neighborhood characteristics (neighborhood racial composition, residential mobility, and rurality). Results: During follow-up, 2,353 (1,347 non-Hispanic White, 1,006 non-Hispanic Black) women died from breast cancer. Living in the most deprived neighborhoods was associated with a 30% increased risk of breast cancer mortality (quintile 5 vs. 1: HR=1.30, 95% CI 1.13-1.49). The association was present among non-Hispanic White (quintile 5 vs. 1: HR=1.47, 95% CI 1.20-1.79) but not non-Hispanic Black women. We observed similar race-specific patterns when assessing jointly stratified associations. For example, among non-Hispanic White women, neighborhood deprivation was associated with breast cancer mortality irrespective of the additional neighborhood characteristics considered, with the strongest association observed among non-Hispanic White women living in the most deprived rural neighborhoods compared to those living in the least deprived urban neighborhoods (HR=1.70, 95% CI 1.30-2.22). In contrast, no association was found among non-Hispanic Black women in any strata of neighborhood racial composition, residential mobility, or rurality (non-Hispanic Black women living in the most deprived rural neighborhoods vs. those living in the least deprived urban neighborhoods: HR=1.05, 95% CI 0.78-1.41). Conclusions: Consistent with previous studies, our study found that living in a deprived neighborhood may increase breast cancer mortality among non-Hispanic White but not non-Hispanic Black women. Neighborhood racial composition, residential mobility, and rurality did not explain the lack of association among non-Hispanic Black women. Other factors beyond neighborhood may contribute to the high breast cancer mortality rate among this racial group. Citation Format: Lauren E. Barber, Leah Moubadder, Maret L. Maliniak, Jasmine M. Miller-Kleinhenz, Jeffrey M. Switchenko, Lauren E. McCullough. Understanding the relationship between neighborhood deprivation and breast cancer mortality among Black and White women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B077.

Abstract A034: How we learn from Black TNBC patients to act for equitable and unbiased care

Abstract Background: Black women are at higher risk for early onset and increased breast cancer mortality, especially from the sub-type Triple-Negative Breast Cancer (TNBC), than their white peers. A patient experience survey has not been implemented or published for Black women diagnosed with TNBC. Tigerlily Foundation (TLF) conducted a TNBC survey of BIack women to understand the patient experience throughout the cancer continuum of care. Methods: The survey instrument received an IRB exception and included 40 questions organized by the following themes: Demographics, Self-Detection/Early Assessment, Screening to Diagnosis, Diagnosis to Treatment, Post Treatment and Palliative Care/Survivorship, Emotional Trauma and Mental Health, and Trust/Bias. Data collection occurred between December 2022 and January 2023. Two methodological approaches influenced this innovative study design: 1) a Health Literate and Culturally Sensitive approach and 2) a Trusted Outreach approach. The survey was sent to leaders of patient-based organizations who shared the TLF survey with their constituents. Results: All participants (N = 106) racially identified as Black women diagnosed with TNBC. The age of participants ranged from 25 – 71. Participants were not always given information to manage their expectations before or after the screening process, as 38% reported they did not receive such information, while 45% reported they did. The number of times participants required diagnostic imaging ranged from only once (24%), two-three times (41%), four-five times (17%), or greater than six times (11%). Biopsies also varied among participants from one (25%), two-three times (40%), four-five times (15%), or greater than six times (8%). Biomarker testing was not equitably offered to all participants, as 30% reported they were not given the opportunity, while 48% were given the choice. While most participants reported a good understanding of their prognosis and treatment options (59%), other participants shared that the information they received could have been better (26%). Others stated they were given zero information to work with (15%). Many participants experienced a diagnosis change, and 57% were initially diagnosed with a different breast cancer subtype, while 24% were initially diagnosed with TNBC. Conclusions: Prospective implementation science is needed to ensure equitable care standards are sustainably provided to Black women. It is imperative to understand the cancer care continuum from the perspective of the patients, what they think of the care received and what education, resources and care they would have liked to receive before or upon diagnosis. Health equity is not achieved based on EHR, county-level beneficiary data, or SEER data alone. Gathering patient experience information is a factor in achieving health equity. TLF successfully reached Black TNBC patients to share their authentic experiences and provided a framework for other research institutions and patient advocacy groups to do the same. Citation Format: Virginia Leach, Jeanne Regante, Maimah Karmo, Lizzie Wittig. How we learn from Black TNBC patients to act for equitable and unbiased care [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A034.

Estimating disparities in breast cancer screening programs towards mortality, case fatality, and DALYs across BRICS-plus

BackgroundNumerous studies over the past four decades have revealed that breast cancer screening (BCS) significantly reduces breast cancer (BC) mortality. However, in BRICS-plus countries, the association between BCS and BC case fatality and disability are unknown. This study examines the association of different BCS approaches with age-standardized mortality, case-fatality, and disability-adjusted life years (DALYs) rates, as well as with other biological and sociodemographic risk variables, across BRICS-plus from a national and economic perspective.MethodsIn this ecological study applying mixed-effect multilevel regression models, a country-specific dataset was analyzed by combining data from the Global Burden of Disease study 2019 on female age-standardized BC mortality, incidence, and DALYs rates with information on national/regional BCS availability (against no such program or only a pilot program) and BCS type (only self-breast examination (SBE) and/or clinical breast examination (CBE) [SBE/CBE] versus SBE/CBE with mammographic screening availability [MM and/or SBE/CBE] versus SBE/CBE/mammographic with digital mammography and/or ultrasound (US) [DMM/US and/or previous tests] in BRICS-plus countries.ResultsCompared to self/clinical breast examinations (SBE/CBE) across BRICS-plus, more complex BCS program availability was the most significant predictor of decreased mortality [MM and/or SBE/CBE: − 2.64, p < 0.001; DMM/US and/or previous tests: − 1.40, p < 0.001]. In the BRICS-plus, CVD presence, high BMI, second-hand smoke, and active smoking all contributed to an increase in BC mortality and DALY rate. High-income and middle-income regions in BRICS-plus had significantly lower age-standardized BC mortality, case-fatality, and DALYs rates than low-income regions when nationwide BC screening programs were implemented.ConclusionsThe availability of mammography (digital or traditional) and BCS is associated with breast cancer burden in BRICS-plus countries, with regional variations. In light of high-quality evidence from previous causal studies, these findings further support the preventive role of mammography screening for BCS at the national level. Intervening on BCS related risk factors may further reduce the disease burden associated with BC.

Providers Respond to USPSTF Report on Screening for Breast Cancer

Providers Respond to USPSTF Report on Screening for Breast Cancer

Increased breast cancer mortality due to treatment delay and needle biopsy type: a retrospective analysis of SEER-medicare

BackgroundSubstantial evidence indicates that delay of first treatment after diagnosis is associated with poorer survival outcomes in breast cancer. Accordingly, the Commission on Cancer introduced a quality measure for receipt of therapeutic surgery within 60 days of diagnostic biopsy for stage I–III breast cancer patients in the non-neoadjuvant setting. It is unknown, however, what may contribute to mortality associated with treatment delay. Therefore, we investigated whether biopsy type moderates the effect of the mortality risk posed by treatment delay.MethodsRetrospective analysis of 31,306 women with stage I–III breast cancer diagnosed between 2003 and 2013 selected from the SEER-Medicare database was performed to determine whether needle biopsy type [core needle biopsy (CNB) or vacuum-assisted biopsy (VAB)] impacts time to treatment (TTT)-associated survival outcomes. Multivariable Fine-Gray competing risk survival models, adjusted for inverse propensity score weights, were used to determine the association between biopsy type, TTT, and breast cancer-specific mortality (BCSM).ResultsTTT ≥ 60 days was associated with 45% higher risk of BCSM (sHR = 1.45, 95% CI 1.24–1.69) compared to those with TTT < 60 days in stage I–III cases. Independent of TTT, CNB was associated with 28% higher risk of BCSM compared to VAB in stage II–III cases (sHR = 1.28, 95% CI 1.11–1.36), translating to a 2.7% and 4.0% absolute difference in BCSM at 5 and 10 years, respectively. However, in stage I cases, the BCSM risk was not associated with type of biopsy.ConclusionsOur results suggest that treatment delay ≥ 60 days is independently associated with poorer survival outcomes in breast cancer patients. In stage II–III, CNB is associated with higher BCSM than VAB. However, type of biopsy does not underlie TTT-associated breast cancer mortality risk.

Intraoperative Fluorescence Guidance for Breast Cancer Lumpectomy Surgery

BackgroundAlthough lumpectomy and mastectomy provide equivalent survival for patients with breast cancer, local recurrence after lumpectomy increases breast cancer mortality. Positive lumpectomy margins, which imply incomplete tumor removal, are the strongest predictor of local recurrence and are identified days after surgery, necessitating a second surgery.MethodsIn this prospective trial, we assessed margin status with or without pegulicianine fluorescence-guided surgery (pFGS) for stages 0 to 3 breast cancers. To prevent surgeons from performing smaller than standard lumpectomies in anticipation of pFGS assistance, patients were randomly assigned 10:1 to pFGS or control groups, thus randomization was not designed to provide a control group for evaluating device performance. In patients undergoing pFGS, additional pFGS-guided cavity margins were excised at sites of pegulicianine signal. We evaluated three coprimary end points: the percentage of patients for whom pFGS-guided margins contained cancer, sensitivity, and specificity.ResultsOverall, 406 patients received 1.0 mg/kg intravenous pegulicianine followed by lumpectomy. Among 392 patients randomly assigned, 316 had invasive cancers, and 76 had in situ cancers. In 27 of 357 patients undergoing pFGS, pFGS-guided margins removed tumor left behind after standard lumpectomy, 22 from cavity orientations deemed negative on standard margin evaluation. Second surgeries were avoided by pFGS in 9 of 62 patients with positive margins. On per-margin analysis, pFGS specificity was 85.2%, and sensitivity was 49.3%. Pegulicianine administration was stopped for adverse events in six patients. Two patients had grade 3 serious adverse events related to pegulicianine.ConclusionsThe use of pFGS in breast cancer surgery met prespecified thresholds for removal of residual tumor and specificity but did not meet the prespecified threshold for sensitivity. (Funded by Lumicell, Inc. and the National Institutes of Health; Clinicaltrials.gov number, NCT03686215.)

Racial and Ethnic Disparities in Locoregional Recurrence Among Patients With Hormone Receptor–Positive, Node-Negative Breast Cancer

Whether racial and ethnic disparities in locoregional recurrence (LRR) exist among patients with similar access to care treated in randomized clinical trials is unknown. To examine racial and ethnic differences in LRR among patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (ERBB2 [formerly HER2 or HER2/neu])-negative, node-negative breast cancer enrolled in the Trial Assigning Individualized Options for Treatment (TAILORx). This unplanned retrospective post hoc analysis examined a prospective multicenter clinical trial population of women with breast cancer enrolled between 2006 and 2010, with 9 years of follow-up. The TAILORx investigators randomized patients to treatment based on their Oncotype DX recurrence score, including endocrine therapy alone (recurrence score <11), endocrine therapy alone vs chemotherapy followed by endocrine therapy (recurrence score 11-25), or chemotherapy followed by endocrine therapy (recurrence score >25). Patients with unknown race and ethnicity or lack of follow-up were excluded from this analysis. Data analysis was performed between December 2021 and March 2022. Locoregional recurrence was defined as ipsilateral in breast, skin, chest wall, or regional nodal recurrence without concurrent distant recurrence, and was stratified by racial and ethnic group. Unadjusted Kaplan-Meier and adjusted Cox proportional hazards regression models were used for survival analyses. Of the 10 273 women enrolled in TAILORx, this analysis included 9369 with T1-2N0 HR-positive, ERBB2-negative breast cancer. Of these patients, 428 (4.6%) were Asian, 886 (9.4%) were Hispanic, 676 (7.2%) were non-Hispanic Black (hereinafter Black), and 7406 (78.8%) were non-Hispanic White (hereinafter White). Assigned treatment receipt was high, with a 9.3% (n = 870) crossover of treatment groups and a median endocrine therapy duration of longer than 60 months, ranging from 61.1 to 65.9 months, across racial and ethnic groups. A total of 6818 patients (72.6%) received radiation (6474 [96.1%] after breast-conserving surgery and 344 [13.0%] after mastectomy). At a median follow-up of 94.8 months (range, 1-138 months), 8-year LRR rates were 3.6% (95% CI, 1.6%-5.6%) in Asian patients, 3.9% (95% CI, 2.2%-5.4%) in Black patients, 3.1% in Hispanic patients (95% CI, 1.7%-4.5%), and 1.8% (95% CI, 1.5%-2.3%) in White patients (P < .001). In survival analyses adjusted for patient, tumor, and treatment factors, Asian race (hazard ratio, 1.91 [95% CI, 1.12-3.29]) and Black race (1.78 [1.15-2.77]) were independently associated with LRR. In adjusted survival analyses for breast cancer mortality, LRR was independently associated with increased breast cancer mortality (hazard ratio, 5.71 [95% CI, 3.50-9.31]). In this post hoc analysis, racial and ethnic differences in LRR were observed among patients with T1-2N0 HR-positive, ERBB2-negative breast cancer despite high rates of treatment receipt in this clinical trial population, with the highest LRR rates in Asian and Black patients. Further study is needed to understand whether failure to rescue after LRR may contribute to racial disparities in breast cancer mortality. ClinicalTrials.gov Identifier: NCT00310180.

Social Isolation Activates Dormant Mammary Tumors, and Modifies Inflammatory and Mitochondrial Metabolic Pathways in the Rat Mammary Gland.

Although multifactorial in origin, one of the most impactful consequences of social isolation is an increase in breast cancer mortality. How this happens is unknown, but many studies have shown that social isolation increases circulating inflammatory cytokines and impairs mitochondrial metabolism. Using a preclinical Sprague Dawley rat model of estrogen receptor-positive breast cancer, we investigated whether social isolation impairs the response to tamoxifen therapy and increases the risk of tumors emerging from dormancy, and thus their recurrence. We also studied which signaling pathways in the mammary glands may be affected by social isolation in tamoxifen treated rats, and whether an anti-inflammatory herbal mixture blocks the effects of social isolation. Social isolation increased the risk of dormant mammary tumor recurrence after tamoxifen therapy. The elevated recurrence risk was associated with changes in multiple signaling pathways including an upregulation of IL6/JAK/STAT3 signaling in the mammary glands and tumors and suppression of the mitochondrial oxidative phosphorylation (OXPHOS) pathway. In addition, social isolation increased the expression of receptor for advanced glycation end-products (RAGE), consistent with impaired insulin sensitivity and weight gain linked to social isolation. In socially isolated animals, the herbal product inhibited IL6/JAK/STAT3 signaling, upregulated OXPHOS signaling, suppressed the expression of RAGE ligands S100a8 and S100a9, and prevented the increase in recurrence of dormant mammary tumors. Increased breast cancer mortality among socially isolated survivors may be most effectively prevented by focusing on the period following the completion of hormone therapy using interventions that simultaneously target several different pathways including inflammatory and mitochondrial metabolism pathways.

Abstract PD1-03: Neighborhood deprivation and breast cancer mortality among Black and White women

Abstract Background: Neighborhood deprivation is hypothesized as a potential driver of racial disparities in breast cancer mortality. However, research shows that neighborhood deprivation is associated with increased breast cancer mortality among White women, but has little to no association among Black women. No study has previously considered the intersections of race, social cohesion, or urban/rural status in the association between neighborhood deprivation and breast cancer mortality. Methods: Neighborhood deprivation was examined in relation to breast cancer mortality among 31,358 non-Hispanic Black and non-Hispanic White women diagnosed with invasive breast cancer (stage I-IIIA) between 2010-2017, followed through 2019, and identified by the Georgia Cancer Registry. Two composite scores, the Area Deprivation Index (ADI) and neighborhood deprivation index (NDI), were used to characterize neighborhood deprivation. A third composite score, the Yost index, was assessed as a measure of neighborhood socioeconomic status (SES). Each composite score was composed of factors representing six domains: poverty, income, occupation, housing, employment, and education. Data on ADI were obtained from the Neighborhood Atlas and was assessed in deciles. American Community Survey data from 2011-2015 and principal components analysis were used to derive the NDI and Yost index. Both measures were assessed in quartiles. Each composite variable was measured at the block group level and linked to patient data. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between each composite variable and breast cancer mortality, overall and by race/ethnicity. Intersectionality will be examined by considering the joint effects of race/ethnicity, social cohesion, and urban/rural status. Results: During the 9-year follow-up period, 2,353 (1,347 non-Hispanic White, 1,006 non-Hispanic Black) women died from breast cancer. Regardless of which composite score was assessed, living in the most deprived or lowest SES neighborhoods was associated with an increased risk of breast cancer mortality in models adjusted for age and race (ADI decile 10 vs. 1: HR=1.57, 95% CI 1.26-1.96; NDI quartile 4 vs. 1: HR=1.43, 95% CI 1.26-1.63; Yost index quartile 1 vs 4: HR= 1.34, 95% CI 1.18-1.51). Stratification by race/ethnicity showed associations were slightly stronger among non-Hispanic White women but null among non-Hispanic Black women. Results from analyses examining the joint effects of race/ethnicity, social cohesion, and urban/rural status are forthcoming and will be presented in December. Conclusions: Consistent with previous studies, our study found that living in a deprived neighborhood may increase breast cancer mortality among non-Hispanic White women, but not non-Hispanic Black women. Investigating the association with an intersectionality framework may help identify subgroups of women who are particularly susceptible to the adverse impact of neighborhood deprivation on breast cancer mortality. Citation Format: Lauren E. Barber, Jasmine M. Miller-Kleinhenz, Maret L. Maliniak, Leah Moubadder, Jeffrey Switchenko, Lauren E. McCullough. Neighborhood deprivation and breast cancer mortality among Black and White women [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD1-03.

Abstract P6-03-02: Social determinants, food deserts, and their combined contribution to breast cancer mortality

Abstract Recent studies have found that both food deserts (FD) and lower socio-economic status (SES) are individually associated with increased breast cancer mortality in the US. However, further work is needed to investigate their combined contribution to breast cancer mortality. Furthermore, valid inference for area-level disease mapping requires careful consideration of spatial clustering. In our study, we utilize data from the USDA Food Access Research Atlas and the American Community Survey. Breast cancer mortality data come from the National Center of Health Statistics 2014 report. We consider a latent class mixture model to determine deprivation categories which incorporate six SES proportion variables (no car, poverty, no HS graduation, crowded housing, unemployment, crowded housing), two FD (Low income and &amp;gt; 1 mile from supermarket and receiving snap benefits and &amp;gt; 1 mile from supermarket) variables. Our latent class model has three levels: Low, Moderate, and High, making up 36.6%, 45.6%, and 17.8% of US counties, respectively. We then incorporated these levels as a fixed effect in a Bayesian hierarchical spatial negative binomial model using R-INLA. In this model, we account for both spatially structured and unstructured effects. Counties classified as “High” on our deprivation categories were associated with a 50% increase in breast cancer mortality rates (95% CrI: [1.12, 2.02]). Also, the county proportion of women &amp;gt;65 was significantly associated with 1.42 times higher breast cancer mortality (95% CrI [1.37, 1.42]). Policies that allow for access in the face of deprivation may contribute to lower overall breast cancer mortality. Citation Format: Kara McCormack. Social determinants, food deserts, and their combined contribution to breast cancer mortality [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-03-02.

Abstract P4-07-31: A whole food, plant-based (WFPB) dietary intervention to improve cardiometabolic and cancer-related outcomes in women with breast cancer

Abstract Background: With dramatically rising obesity rates in the US, obesity at breast cancer diagnosis is common; further compounding the problem is that breast cancer treatment often results in additional weight gain. Among women undergoing breast cancer treatment, both obesity at diagnosis and post-diagnosis weight gain are associated with increased all-cause mortality and increased breast cancer mortality. We tested a WFPB dietary intervention in metastatic breast cancer patients to improve cardiometabolic and cancer-related outcomes, as it has been shown to reduce weight and improves cardiometabolic health in overweight and obese individuals. Methods: Women with stage 4 breast cancer receiving treatment were randomized 2:1 into 2 arms: 1) a WFPB diet (N=21) or 2) usual diet (N=11) for 8 weeks with assessments at baseline, 4, and 8 weeks. Our WFPB diet consisted of an ad libitum whole food, plant-based diet; 3 meals/day were provided to WFPB subjects, which included fruits, vegetables, whole grains, nuts and seeds, and excluded meat, dairy, eggs, and added oils/solid fats. WFPB subjects received weekly education regarding diet. Subjects in the usual care group were asked to continue their usual diet for the next 8 weeks. Outcomes include cardiometabolic risk factors, related sex hormones, and cancer progression markers. Effects of the WFPB diet on the outcomes were assessed by comparing marginal means by arm estimated at 8 weeks from the analysis of covariance model controlling for the baseline value. Results: Of the 32 subjects randomized, 30 subjects (20 WFPB and 10 usual care) completed all 3 assessments. Reductions in weight, BMI, total cholesterol, and LDL cholesterol were statistically significant as well as clinically meaningful, both within the WFPB group and between the groups. In the WFPB group, subjects lost a mean of 6.2% of their body weight versus 0.7% body weight loss in the control group (p&amp;lt; 0.01). LDL cholesterol was reduced by a mean of 20.0% in the WFPB subjects versus a 10.6% increase in control subjects (p&amp;lt; 0.01). Reductions in insulin and HOMA-IR, a measure of insulin sensitivity, were statistically significant within the WFPB group and trended towards significance between the groups. Sex hormone binding globulin (SHBG) levels increased significantly both within the WFPB group and between groups. There was a significant decrease in both IGF-1 and free testosterone within the WFPB group from baseline to week 8. Conclusions: Our WFPB intervention resulted in improvements in several cardiometabolic and hormonal markers. The intentional weight loss, which was clinically large given the duration of the trial, was accompanied by reduced cholesterol, insulin resistance, free testosterone, and IGF-1. Given the moderate to large effect sizes noted, further study is warranted to evaluate the sustainability of benefits over time and to assess their potential impact on cancer-related outcomes. Table 1: Cardiometabolic and Cancer-Related Outcomes Citation Format: Erin Campbell, Thomas Campbell, Eva Culakova, Nellie Wixom, Joseph Guido, Lisa Blanchard, James Fetten, Michelle Janelsins, Karen Mustian, Luke Peppone. A whole food, plant-based (WFPB) dietary intervention to improve cardiometabolic and cancer-related outcomes in women with breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-31.

Evaluation of Lee-Carter model to breast cancer mortality prediction in China and Pakistan.

Precise breast cancer-related mortality forecasts are required for public health program and healthcare service planning. A number of stochastic model-based approaches for predicting mortality have been developed. The trends shown by mortality data from various diseases and countries are critical to the effectiveness of these models. This study illustrates the unconventional statistical method for estimating and predicting the mortality risk between the early-onset and screen-age/late-onset breast cancer population in China and Pakistan using the Lee-Carter model. Longitudinal death data for female breast cancer from 1990 to 2019 obtained from the Global Burden of Disease study database were used to compare statistical approach between early-onset (age group, 25-49 years) and screen-age/late-onset (age group, 50-84 years) population. We evaluated the model performance both within (training period, 1990-2010) and outside (test period, 2011-2019) data forecast accuracy using the different error measures and graphical analysis. Finally, using the Lee-Carter model, we predicted the general index for the time period (2011 to 2030) and derived corresponding life expectancy at birth for the female breast cancer population using life tables. Study findings revealed that the Lee-Carter approach to predict breast cancer mortality rate outperformed in the screen-age/late-onset compared with that in the early-onset population in terms of goodness of fit and within and outside forecast accuracy check. Moreover, the trend in forecast error was decreasing gradually in the screen-age/late-onset compared with that in the early-onset breast cancer population in China and Pakistan. Furthermore, we observed that this approach had provided almost comparable results between the early-onset and screen-age/late-onset population in forecast accuracy for more varying mortality behavior over time like in Pakistan. Both the early-onset and screen-age/late-onset populations in Pakistan were expected to have an increase in breast cancer mortality by 2030. whereas, for China, it was expected to decrease in the early-onset population. The Lee-Carter model can be used to estimate breast cancer mortality and so to project future life expectancy at birth, especially in the screen-age/late-onset population. As a result, it is suggested that this approach may be useful and convenient for predicting cancer-related mortality even when epidemiological and demographic disease data sets are limited. According to model predictions for breast cancer mortality, improved health facilities for disease diagnosis, control, and prevention are required to reduce the disease's future burden, particularly in less developed countries.

Population-based temporal trends and ethnic disparity in breast cancer mortality in South Africa (1999-2018): Joinpoint and age-period-cohort regression analyses.

Joinpoint regression analyses of the trends in crude and age-standardized mortality rates (ASMR) of breast cancer among South African women were conducted from 1999 to 2018 using mortality data from Statistics South Africa. Age-period-cohort regression analysis was then conducted to evaluate the independent effect of age, period, and cohort on breast cancer mortality, and analysis was stratified by ethnicity. The mortality rate of breast cancer (from 9.82 to 13.27 per 100,000 women) increased at around 1.4% per annum (Average Annual Percent Change (AAPC): 1.4%, 95% CI:0.8-2.0, P-value< 0.001). Young women aged 30-49 years (1.1%-1.8%, P-value< 0.001) had increased breast cancer mortality. The risk of breast cancer mortality increased among successive birth cohorts from 1924 to 1928 but decreased among recent cohorts born from 1989 to 1993. In 2018, the breast cancer mortality rate among Blacks (9.49/100,000 women) was around half of the rates among the non-Blacks. (Coloreds: 18.11 per 100,000 women; Whites: 17.77/100,000 women; Indian/Asian: 13.24 per 100,000 women). Contrary to the trends in high- and middle-income countries, breast cancer mortality increased in South Africa especially among young women. Breast cancer prevention programs should be intensified and should also target young women. The marked disparity in ethnic burden of breast cancer should be considered during planning and implementation of interventions.

Abstract C093: Historical redlining is associated with breast cancer subtype, stage at diagnosis and mortality

Abstract Background: Structurally racist policies have an important impact on health. The etiologic basis of racial disparities in aggressive forms of breast cancer is not well understood. Few studies have investigated the impact of structural racism as a potential driver of etiologic heterogeneity. We sought to estimate the effect of historic redlining on the development of aggressive subtypes and late-stage disease, and examine its role in breast cancer mortality. Methods: Using the Georgia Cancer Registry, we identified 921 non-Hispanic White (NHW) and 878 non-Hispanic Black (NHB) women residing in a Georgia Home Owners' Loan Corporation (HOLC) graded area with a first primary invasive breast cancer diagnosis in 2010–2017. Historic redlining scores for 2010 census tracts were calculated according to the proportion of HOLC grades within the tract. Historic redlining scores were examined continuously and dichotomized at &amp;lt;2.5, which represents areas that were historically considered low for investment risk (Green/“Best” or Blue/“Still Desirable”), vs. ≥2.5, which represents areas that were considered to be high risk (Yellow/“Definitely Declining” or Red/“Hazardous”). We used age-adjusted logistic regression to calculate case-only odds ratios (ORs) and 95% confidence intervals (CIs) associating historically high-risk redlined areas to a diagnosis of Luminal B, HER2, or Triple-Negative breast cancer (TNBC) compared with Luminal A tumors and a diagnosis of Stage II, III, or Stage IV breast cancer compared with Stage I disease. Additionally, we used Cox proportional hazards regression to calculate age-adjusted hazard ratios (HRs) and 95% CIs to associate historically high-risk areas with breast cancer mortality, overall and within each race strata. Results: Overall, 81% of NHB and 19% of NHW women lived in historically redlined census tracts. Women living in redlined areas were diagnosed with more aggressive subtypes (TNBC and HER2) and later stage (Stage III and IV) breast cancers. Compared with Luminal A breast cancer, the ORs for living in historically high-risk vs. low risk investment areas were 2.05 (95%CI=1.44, 2.93) for TNBC and1.49 (95%CI=0.89, 2.48) for HER2 disease. Compared with Stage I breast cancers, the ORs for historically high-risk vs. low risk investment areas were 1.85(95%CI=1.30, 2.63) for Stage III and 2.00 (95%CI=1.32, 3.02) for Stage IV breast cancer. Residing in historically high-risk census tracts was associated with a 1.68-fold increase in breast cancer mortality (95% CI=1.23, 2.30), after adjusting for age. The association was most pronounced among NHW women living in redlined census tracts (HR=1.36; 95%CI=0.99, 1.87); a near-null association was observed among NHB women (HR=0.97; 95% CI=0.78, 1.20). Conclusions: Historic redlining scores were associated with the diagnosis of more aggressive forms of breast cancer and breast cancer mortality. Historic place-based measures of structural racist policies have modern-day implications on health outcomes and may underpin reported disparities in aggressive or advanced tumor types. Citation Format: Jasmine M. Miller-Kleinhenz, Maret L. Maliniak, Micah J. Streiff, Leah Moubadder, Lauren E. Barber, Rebecca Nash, Lindsay J. Collin, Jeffrey M. Switchenko, Kevin C. Ward, Lauren E. McCullough. Historical redlining is associated with breast cancer subtype, stage at diagnosis and mortality [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C093.

Abstract 3672: Area-level drivers of the breast cancer mortality race disparity in Georgia

Abstract In the US, breast cancer mortality is 40% greater among Black than White women. The mortality disparity varies geographically and has persisted despite improvements in survival. Georgia is one of six states where breast cancer recently surpassed lung cancer as the leading cause of cancer death among Black but not White women, is a large and diverse state, and thus, an ideal setting to study race disparities. Our work in the Atlanta Metro area has shown that the mortality disparity is pronounced among patients with clinically favorable subtypes, low Oncotype DX® recurrence scores, guideline-concordant care, and similar access to surgical facilities. The disparity also persists among patients with private insurance and those living in areas of low poverty, suggesting clinical and sociodemographic differences do not fully account for the observed disparity. Recent evidence suggests area-level factors may contribute to the disparity. Our group reported that neighborhood-level redlining (i.e., mortgage denial based on place) is associated with an increase in breast cancer mortality while neighborhood-level lending bias (i.e., mortgage denial based on race) is associated with a decrease in breast cancer mortality. In Atlanta, Black patients are more likely to live in redlined areas and less likely to live in areas with lending bias, than White patients, further suggesting place is an important driver of disparities. We investigated the role of other area-level factors on race-specific mortality in Georgia. Race-specific standardized mortality ratios were computed for each county in Georgia. Observed breast cancer deaths among non-Hispanic White (NHW) and non-Hispanic Black (NHB) women within 5 years of a stage I-III breast cancer diagnosis (2005-2013) were obtained from the Georgia Cancer Registry. County-level characteristics were derived from the American Community Survey and Georgia Department of Public Health. A Bayesian model-based approach was used to stabilize local estimates and estimate associations with area-level factors. Smoothed estimates of relative disparity ranged from 1.2 to 1.7, with pronounced disparity for counties surrounding the Atlanta and Savannah metropolitan areas and least pronounced disparity in Metro Albany counties. Among NHB women, living in a rural (versus non-rural) county was associated with a nearly 20% increase in breast cancer mortality (RR=1.19, 95% credible interval (CI): 0.96, 1.48); an association not observed in NHW patients (RR=0.93, 95% CI: 0.79, 1.07). In contrast, a 10-point increase in the percent of adults with ≤high school education was associated with a 10% increase (95% CI: 1.05, 1.17) in mortality for NHW patients only. The race disparity in Georgia is not evenly distributed across counties. We identified area-level characteristics associated with race-specific mortality. Identifying other area-level drivers of breast cancer mortality is an important area of inquiry. Citation Format: Rebecca Nash, Lindsay J. Collin, Jeffrey Switchenko, Lauren E. McCullough. Area-level drivers of the breast cancer mortality race disparity in Georgia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3672.

Hormone Replacement Therapy After Breast Cancer: It Is Time.

This article reviews the decades of evidence supporting the reproducible benefits of HRT for menopausal symptom control, improved cardiac health, prevention of hip fracture, reduction in the risk and pace of cognitive decline, and enhanced longevity. It quantifies the increased risk of thromboembolism associated with oral, though not transdermal, HRT. It evaluates the repeated claims that HRT is associated with an increased risk of breast cancer development, and, when administered to breast cancer survivors, an increased risk of breast cancer recurrence. Twenty-five studies of HRT after a breast cancer diagnosis, published between 1980 and 2013, are discussed, as are the 20 reviews of those studies published between 1994 and 2021. Only 1 of the 25 studies, the HABITS trial, demonstrated an increased risk of recurrence, which was limited to local or contralateral, and not distant, recurrence. None of the studies, including HABITS, reported increased breast cancer mortality associated with HRT. Even in the HABITS trial, the absolute increase in the number of women who had a recurrence (localized only) associated with HRT administration was 22. It is on the basis of these 22 patients that HRT, with its demonstrated benefits for so many aspects of women's health, is being denied to millions of breast cancer survivors around the world.

Abstract P3-12-02: Loss of PTEN expression, PIK3CA mutations, and breast cancer survival in the Nurses’ health studies

Abstract Background: PTEN loss and/or PIK3CA mutation are hypothesized to predict more aggressive tumor behavior and worse outcomes in women with breast cancer. However, the results of previous studies with small sample size have been conflicting. Methods: We followed pre- and postmenopausal women with invasive breast cancer from the Nurses’ Health Study (diagnosed 1976-2011) and Nurses’ Health Study II (1989-2011) with data available on PTEN cytoplasmic expression (n=4316, breast cancer-specific deaths=777) and/or PIK3CA mutation (n=2930, breast cancer-specific deaths=317). PTEN protein expression was evaluated by immunohistochemistry and scored as a digitally quantified continuous measure (1-100%). Polymerase chain reaction and pyrosequencing of six hot spot mutations of PIK3CA were performed on DNA extracted from formalin-fixed paraffin-embedded tumors. Information on other covariates was self-reported at baseline and repeatedly measured with follow-up questionnaires every two to four years. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between loss of PTEN expression and/or PIK3CA mutation and breast cancer-specific mortality were estimated using Cox proportional hazards regression models. Results: In this large epidemiological study, the loss of tumor cell PTEN cytoplasmic staining expression (≤10%) occurred in 17.6% of cases, and the overall mutation of PIK3CA occurred in 10.8% of cases. After adjusting for tumor characteristics, treatment, and lifestyle factors, the loss of PTEN expression (versus expression &amp;gt;10%) was not associated with worse breast cancer survival among overall samples (HR =0.85; 95%CI=0.71-1.03) and among estrogen receptor (ER)-positive tumors (HR =1.11; 95%CI=0.84-1.47). However, among women with ER-negative tumors, PTEN expression loss was strongly associated with lower breast cancer mortality (HR =0.68; 95%CI=0.48-0.96). Overall mutation status of PIK3CA was not associated with breast cancer mortality (HR =1.06; 95%CI=0.78-1.45). Combining PTEN and PIK3CA status, compared with tumors without PTEN loss and without PIK3CA mutation (wild type), those with PTEN loss and/or PIK3CA mutation were not at higher risk (HR =1.05; 95%CI=0.85-1.32). However, women with PTEN loss and PIK3CA mutation jointly (n=39, breast cancer-specific deaths=15) had increased breast cancer mortality (HR =2.05; 95%CI=1.07-3.94). Conclusion: This study is the largest to date examining PTEN and PIK3CA status and breast cancer survival, in which we found that the prognostic value of PTEN status differed by ER status, and the joint status of PTEN loss of expression and PIK3CA mutation was associated with worse breast cancer survival. Citation Format: Tengteng Wang, Yujing J Heng, Gabrielle M Baker, Vanessa C Bret-Mounet, Susan E Hankinson, Michelle D Holmes, Wendy Y. Chen, Walter C. Willett, Bernard A. Rosner, Rulla M Tamimi, A. Heather Eliassen. Loss of PTEN expression, PIK3CA mutations, and breast cancer survival in the Nurses’ health studies [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-12-02.